CN112577917A - Method for detecting colored impurities in tigecycline for injection - Google Patents
Method for detecting colored impurities in tigecycline for injection Download PDFInfo
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- CN112577917A CN112577917A CN202011577477.8A CN202011577477A CN112577917A CN 112577917 A CN112577917 A CN 112577917A CN 202011577477 A CN202011577477 A CN 202011577477A CN 112577917 A CN112577917 A CN 112577917A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
- G01N21/3151—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths using two sources of radiation of different wavelengths
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
- G01N2021/3155—Measuring in two spectral ranges, e.g. UV and visible
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Abstract
The invention provides a method for detecting colored impurities in tigecycline for injection. The detection method adopts an ultraviolet-visible spectrophotometry method to detect whether the tigecycline for injection contains colored impurities, wherein the detection wavelength used by the ultraviolet-visible spectrophotometry method is 609-629 nm. The tigecycline colored impurity has obvious absorption at 609-629nm, and has a larger difference with the light absorption wavelength of the tigecycline API, so that the influence of the tigecycline API can be avoided, and the accuracy and the qualification of the tigecycline colored impurity are further provided.
Description
Technical Field
The invention relates to the field of drug analysis, in particular to a method for detecting colored impurities in tigecycline for injection.
Background
A patent published by the original tigecycline manufacturer, hui-shi 2009 (US 20090097026) studied colored impurities of tigecycline. The patent example experiment 5 shows that tigecycline solution generates colored impurities through oxidative degradation at room temperature, the colored impurities are blue substances, and the research shows that the colored impurities are not single components but are mixtures consisting of a plurality of substances, wherein at least tigecycline ring-opening substances are included. Tigecycline API was orange and the sample solution was visually observed to appear green after oxidative degradation.
The colored impurity tigecycline open-loop substance can be prepared by degradation, separation and purification, and the generation mechanism is as follows:
the existing commercial sample implements an impurity absorbance method in the standard YBH05372018 to detect colored impurities in tigecycline, and specifically comprises the steps of taking 1 bottle of the product, adding 1mol/L of a hydrochloric acid methanol solution to prepare a solution containing 10mg of tigecycline per 1ml, and measuring the absorbance at 490nm wavelength by an ultraviolet-visible spectrophotometry (0401 in the four general rules of the Chinese pharmacopoeia 2015 edition). However, the original YBH05372018 standard does not fully research the generation mechanism of colored impurities and the selection of the measuring wavelength, and 490nm is selected as the detecting wavelength by directly referring to the method of 'impurity absorbance' of tetracycline drug doxycycline hydrochloride in Chinese pharmacopoeia. The existing research results show that the tigecycline API at 490nm has strong absorption, seriously interferes with the determination of colored impurities, and is not suitable for the detection of the colored impurities.
Disclosure of Invention
The invention mainly aims to provide a method for detecting colored impurities in tigecycline for injection, so as to solve the problem that the detection result of the method for detecting colored impurities in tigecycline in the prior art is inaccurate.
In order to achieve the purpose, according to one aspect of the invention, a method for detecting colored impurities in tigecycline for injection is provided, wherein an ultraviolet-visible spectrophotometry method is adopted to detect whether the tigecycline for injection contains the colored impurities, wherein the detection wavelength used by the ultraviolet-visible spectrophotometry method is 609-629 nm.
Further, the detection method comprises the following steps: step S1, re-dissolving tigecycline for injection by using a solvent to form a sample to be detected; and step S2, detecting the sample to be detected by adopting an ultraviolet-visible spectrophotometry to obtain the absorbance of the corresponding colored impurities.
Further, the solvent is purified water.
Further, the solvent is a 10% acetonitrile aqueous solution.
Further, the solvent is 0.9% sodium chloride injection.
Further, the solvent is 5% glucose injection.
Further, the solvent is ringer's lactate.
Further, the content of tigecycline for injection in the sample to be detected is 8-12 mg/mL.
Further, the colored impurities include tigecycline ring openers.
By applying the technical scheme, experiments show that the colored tigecycline impurity has obvious absorption at 609-629nm and has a larger difference with the light absorption wavelength of the tigecycline API, so that the influence of the tigecycline API can be avoided, and the accurate qualitative of the colored tigecycline impurity is further provided.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:
figure 1 shows a full wavelength scan spectrum of tigecycline API according to example 1 of the present invention;
FIG. 2 shows a full wavelength scan spectrum of a blank adjuvant (lactose) according to example 1 of the present invention;
FIG. 3 shows graphs of samples obtained after different standing times using different degrees of oxidative damage samples according to example 2 of the present invention;
FIG. 4 shows a full wavelength scanning spectrum of samples destroyed using different degrees of oxidation according to example 2 of the present invention;
figure 5 shows a full wavelength scan of a sample showing reconstitution of a tigecycline ring opened complex using a methanol hydrochloride solution as a solvent according to one embodiment of the present invention; and
figure 6 shows a full wavelength scan of a sample showing reconstitution of a tigecycline ring opened complex using purified water as a solvent according to one embodiment of the present invention.
Detailed Description
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail below with reference to the embodiments with reference to the attached drawings.
As analyzed in the background art of the present application, the YBH05372018 standard method in the prior art adopts 490nm as the detection wavelength, and tigecycline API at 490nm has strong absorption, which seriously interferes with the determination of colored impurities, and is not suitable for the detection of colored impurities. In order to solve the problem, the application provides a method for detecting colored impurities in tigecycline for injection, which is used for detecting whether the tigecycline for injection contains the colored impurities by adopting an ultraviolet-visible spectrophotometry, wherein the detection wavelength used by the ultraviolet-visible spectrophotometry is 609-629 nm.
Experiments show that the colored tigecycline impurity has obvious absorption at 609-629nm and has a larger difference with the light absorption wavelength of the tigecycline API, so that the influence of the tigecycline API can be avoided, and the accurate qualitative of the colored tigecycline impurity is further provided.
The uv-vis spectrophotometry of the present application may be performed by referring to the conventional uv-vis spectrophotometry performing process in the art, and in some embodiments of the present application, it is preferred that the detecting method comprises: step S1, dissolving tigecycline for injection again by adopting a solvent to form a sample to be detected; step S2, detecting the sample to be detected by adopting an ultraviolet-visible spectrophotometry to obtain the absorbance of the corresponding colored impurities
The existing YBH05372018 standard method adopts a methanol hydrochloride solution as a solvent to redissolve tigecycline for injection, but the applicant finds that ring-opening substances of representative substances of colored impurities are unstable in a 1mol/L methanol hydrochloride solution, the maximum absorption wavelength of a full-wavelength scanning graph (figure 5) of the ring-opening substances under related substances is not 640nm under the limit concentration (0.02%), and the maximum absorption wavelength is inconsistent with 640nm in a patent US20090097026 and is presumed to be degraded and damaged. And the solution prepared by re-dissolving purified water as a solvent is scanned at full wavelength, and the maximum absorption wavelength of the ring-opening compound is 640nm (see figure 6), so that the degradation of the ring-opening compound in a hydrochloric acid methanol solution is verified, and the test result is inaccurate. In order to accurately test the content of each colored impurity, the solvent is preferably purified water, 10% acetonitrile water solution, 0.9% sodium chloride injection, 5% glucose injection or lactated ringer's solution. The above solvents are also solvents that have been tested to stabilize the presence of colored impurities, and corresponding examples are provided below.
The higher the concentration of the target object to be detected is, the higher the absorbance is, but the higher the absorbance is, the more accurate the result is, according to experience, the preferable content of the tigecycline for injection in the sample to be detected is 8-12 mg/mL, so that the accurate absorbance is obtained, and a reliable data basis is further provided.
The detection method is suitable for detecting the conventional colored impurities of tigecycline at present, for example, the colored impurities are tigecycline ring openers and the like.
The advantageous effects of the present application will be further described below with reference to examples and comparative examples.
The following examples and comparative examples were conducted in accordance with the YBH05372018 standard, except for the specific descriptions of the detection wavelength, the solvent and the detection object.
Example 1
Specificity verification of wavelength absorption
According to the prescription, appropriate amount of tigecycline API and blank auxiliary material (lactose) are respectively weighed, and the tigecycline API and the blank auxiliary material (lactose) are dissolved in purified water and then scanned at full wavelength as shown in figures 1 and 2. As can be seen from the graphs in FIGS. 1 and 2, the tigecycline API and the blank excipient (lactose) have no absorption in the range of 609-629nm, thereby avoiding the influence on the absorption degree of colored impurities of tigecycline.
Screening for detection wavelengths was performed using samples with varying degrees of oxidative damage. Hydrogen peroxide with the concentration of 1 percent is added into tigecycline sample solution for injection (pure water is taken as a solvent) containing 10mg/ml of tigecycline, the obtained samples are shown in figure 3 after different standing times, full-wavelength scanning is carried out on each sample, and the scanning result under each condition is shown in figure 4. Since more degradation impurities are generated as time goes by, the green color is gradually deepened as time goes by in fig. 3; also shown in FIG. 4 is the increase in absorbance at 619nm with time.
Therefore, 619nm is used as the detection wavelength, so that interference of tigecycline API and blank auxiliary materials (lactose) is avoided, and sensitive and accurate detection of colored impurities of tigecycline is realized.
Example 2
Verification of absorption wavelength
Three batches of tigecycline samples for injection are detected by three wavelengths of 609nm, 619nm and 629nm, wherein water is used as a solvent, and the content of tigecycline in the preparation is 10mg/mL of the samples to be detected. The absorbance of impurities for three samples tested is shown in table 1.
TABLE 1
As can be seen from table 1, the absorbance obtained at the three detection wavelengths fluctuates within a range of 0.002, and there is no significant difference in specific values, and it can be considered that the results are substantially consistent.
Example 3
Validation of solvents
According to the requirements of the usage amount of the original developer specification, samples are respectively redissolved by purified water, 10% acetonitrile water solution, 0.9% sodium chloride injection, 5% glucose injection and lactated ringer's test to form samples to be detected, the content of tigecycline for injection is 10mg/mL, then the samples to be detected are placed for 6 hours at room temperature, and the results are shown in Table 2.
TABLE 2
The data in table 2 show that different compatible solvents do not affect the detection of the absorbance of impurities.
Example 4
And selecting 619nm wavelength to detect three batches of tigecycline samples for injection, wherein water is adopted as a solvent, and the content of tigecycline for injection in the preparation is 8mg/mL, 12mg/mL and 5mg/mL of samples to be detected. The absorbance of impurities for the three samples tested is shown in table 3.
TABLE 3
According to the results, the tigecycline samples in the three batches all contain a certain amount of colored impurities, and the absorbance can be as low as 0.002, which indicates that the method has enough sensitivity.
From the above description, it can be seen that the above-described embodiments of the present invention achieve the following technical effects:
the tigecycline colored impurity has obvious absorption at 609-629nm, and has a larger difference with the light absorption wavelength of the tigecycline API, so that the influence of the tigecycline API can be avoided, and the accurate control of the tigecycline colored impurity is further provided.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. The method for detecting colored impurities in tigecycline for injection is characterized by detecting whether the tigecycline for injection contains the colored impurities by adopting an ultraviolet-visible spectrophotometry, wherein the detection wavelength used by the ultraviolet-visible spectrophotometry is 609-629 nm.
2. The detection method according to claim 1, characterized in that it comprises:
step S1, re-dissolving tigecycline for injection by using a solvent to form a sample to be detected;
and step S2, detecting the sample to be detected by adopting an ultraviolet-visible spectrophotometry method to obtain the absorbance of the corresponding colored impurities.
3. The detection method according to claim 2, wherein the solvent is purified water.
4. The detection method according to claim 2, wherein the solvent is a 10% acetonitrile aqueous solution.
5. The detection method according to claim 2, wherein the solvent is 0.9% sodium chloride injection.
6. The method of claim 2, wherein the solvent is a 5% glucose injection.
7. The detection method according to claim 2, wherein the solvent is ringer's lactate.
8. The detection method according to any one of claims 2 to 7, wherein the content of tigecycline for injection in the sample to be detected is 8-12 mg/mL.
9. The detection method according to claim 1, wherein the colored impurities comprise tigecycline ring openers.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202011577477.8A CN112577917A (en) | 2020-12-28 | 2020-12-28 | Method for detecting colored impurities in tigecycline for injection |
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| CN202011577477.8A CN112577917A (en) | 2020-12-28 | 2020-12-28 | Method for detecting colored impurities in tigecycline for injection |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101340895A (en) * | 2005-12-22 | 2009-01-07 | 惠氏公司 | Oral formulations comprising tigecycline |
| US20090097026A1 (en) * | 2007-10-12 | 2009-04-16 | Wyeth | Color measurements of reconstituted tigecycline and degradant thereof |
| CN101479235A (en) * | 2006-04-24 | 2009-07-08 | 特瓦制药工业有限公司 | Tigeycline crystalline forms and processes for preparation thereof |
-
2020
- 2020-12-28 CN CN202011577477.8A patent/CN112577917A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101340895A (en) * | 2005-12-22 | 2009-01-07 | 惠氏公司 | Oral formulations comprising tigecycline |
| CN101479235A (en) * | 2006-04-24 | 2009-07-08 | 特瓦制药工业有限公司 | Tigeycline crystalline forms and processes for preparation thereof |
| US20090097026A1 (en) * | 2007-10-12 | 2009-04-16 | Wyeth | Color measurements of reconstituted tigecycline and degradant thereof |
Non-Patent Citations (2)
| Title |
|---|
| 李里特: "《食品物性学》", 30 June 2001, 中国农业出版社 * |
| 魏娜 等: "替加环素中有色杂质测定", 《山东化工》 * |
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